title: Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation.
abstract: Piperidinylpyrimidine derivatives, previously prepared as inhibitors of TNF-alpha production, were evaluated for their inhibitory activity against HIV-1 LTR activation. Some of these derivatives inhibited activation of HIV-1 LTR-directed CAT gene expression induced by PMA in Jurkat cells. In this report, we describe SAR in this series of compounds and show that the 3,4-methylenedioxybenzoyl (piperonyloyl) group on the nitrogen of piperidine and lipophilic substitution at the C(6)-position of pyrimidine are important for this inhibitory activity. Some of the synthesized compounds also inhibited HIV-1 LTR transactivation induced by viral protein Tat. These results suggest that piperidinylpyrimidines are useful as potent AIDS therapeutics that directly inhibit HIV-1 LTR activation and indirectly suppress TNF-alpha production.
authors.affiliation: Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan. norio-fujiwara@ds-pharma.co.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ueda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Hajime
authors.initials: H
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha